This is an amended application for the third competing renewal (years 11-15) of the Northern California Childhood Leukemia Study (NCCLS), a population-based, case-control study that currently has ~1,000 childhood leukemia cases and 1,300 matched controls, annotated with extensive environmental data and banked DNA. Approximately 40% of the study population is Hispanic. For this competitive renewal, the investigators propose to evaluate three hypotheses: 1) the risk of childhood ALL and the subtypes B-cell ALL and common ALL are associated with immune function in response to infection early in life, variants in immune function genes, and their joint effects;2) risk of AML, ALL, and specific ALL subtypes are associated with self-reported pre- and post-natal residential exposure to environmental chemicals, variants in xenobiotic transport metabolism genes, and their joint effects;3) risk of AML, ALL, and specific ALL subtypes are associated with calibrated levels of specific VOCs (volatile organic compounds), pesticides, and POPs (persistent organic pollutants), and these associations are modified by variants in xenobiotic transport metabolism genes. Five aims are proposed to test these hypotheses. The first aim is to collect demographic and environmental data and biologic specimens from ~660 new cases of childhood leukemia and 660 matched controls. Aim 2 is to collect home environmental dust and air samples in a stratified random sample of 300 new homes in order to calibrate interview data and household characteristics. Aim 3 is to collect germline genetic data from the existing and new subjects in order to genotype approximately 10K SNPs using a candidate gene approach. Aim 4 is to examine the main effects of genes and environmental exposures for risk of childhood leukemia subtypes, using existing and new data. Aim 5 is to examine gene-environment interactions within the dataset. For each sub-aim, differences in effect by Hispanic status will be assessed. PUBLIC HEALTH RELEVANCE: The multidisciplinary research team in the Northern California Childhood Leukemia Study (NCCLS) proposes to examine how environmental, immune, and genetic risk factors for childhood leukemia interact, and will explore the etiology of rare and understudied subtypes of leukemia. Detailed information on immunity and residential exposures to pesticides, persistent organic pollutants, and benzene will be available for approximately 1,660 leukemia cases and 1,890 matched controls, and biospecimens will be collected to conduct molecular and genetic susceptibility studies. The culturally diverse population of the NCCLS ensures that environmental and genetic exposures unique to Hispanics will be examined.